We are requesting continuing support to study anatomical links between genes and behavior in Williams I Syndrome (WS). The present period of research will continue to refine the testing of hypotheses that have emerged from the synthesis of collective results from the previous period across Projects I-V. The overarching hypothesis stemming from the neurocognitive, anatomical and imaging, neurophysiological, andl genetic findings in WS implicates a disordered establishment of dorsoventral and anteroposterior gradients during the formation of cerebral cortex. The specific hypothesis is that the dorsal caudal cortex is set up and functions abnormally as a direct result of some of the deleted genes, and that ventral and anterior cortices change anatomically and functionally because of it. Thus far anatomical research showed curtailment of the dorsal central sulcus and reduction in dorsocaudal forebrain. At the architectonic level, cell measurements indicated alterations both in dorsal and ventral posterior cortices, but of different types, which is congruenl with neuroimaging results showing curtailement of caudodorsal areas and relative enlargement of frontal and ventral areas. A unique partial deletion case led us to study transcription factors GTF21 and GTF21rd staining in visual cortex, which showed abnormalities in cortex related to the dorsal visual pathway. The specific aims of this component of the Program Project relate to the overarching hypothesis: Thus, we will compare dorsal and ventral cortices caudally and frontally. A corollary hypothesis claims that abnormalities in dorsocaudal brain means that other spatially related cortices, in addition to the spatial visual cortex, will be found to be abnormal. A second corollary is that the abnormal affiliative behavior in WS is related to enhanced development of ventral anterior regions, including the amygdala, the lateral hypothalamus, and relevant frontomedial cortex, which will be one aim in this study, too. Finally, two subcortical nuclei, the LGN and the MGN will be studied with respect to the hypothesis that magnocellular subsystems within these nuclei relate differentially to the dorsocaudal and ventrocaudal cortex. A major aim of the proposed research will be to provide information that will inform research carried out in the behavioral, neurophysiological, imaging, and genetic components of the program project, as well as deriving clues from findings in those project to help guide our research in the present project. The collaboration, thus far, has been productive to a greater degree than the sum of its parts.